Genes and Tyramine Intolerance Part 1: Monoamine Oxidase A

To understand tyramine intolerance better, the Rogue Scientist explores the genes involved in tyramine metabolism. Beginning with monoamine oxidase A.
genes

If you’re reading this article, you probably already know what tyramine intolerance is. You probably also know I have it, and devote at least a certain amount of blogging time to exploring this health topic.

I’ve wanted to write a series on genes and tyramine intolerance. I cover some of this in my book, The Tyramine Intolerance Handbook, but this blog allows me to explore much more, especially as I learn more over time. And… it makes sense to begin with the gene that codes for the most important enzyme involved in the metabolism of tyramine:

Monoamine oxidase A, or MAO-A

But first, a quick primer on why we even talk about genes when it comes to food sensitivity.

Why are Genes Important in Tyramine Intolerance?

Our genes influence everything about us: our appearance, our behavior, and our health. They also play a significant role in food intolerance or sensitivity (not to be confused with food allergy). Why is this?

Food intolerance occurs when the body can’t effectively break down some substance in the foods you eat. The common example I often use is lactose intolerance, the inability to break down lactose, a type of sugar found in milk and dairy products.

But what breaks down lactose? An enzyme called lactase. If there isn’t enough lactase to break down lactose, you get symptoms.

Likewise, tyramine gets broken down by enzymes as well. And when you don’t have enough of those enzymes? Tyramine doesn’t get metabolized properly and that’s when the headaches, blood pressure spikes, palpitations, and anxiety kick in.

But where do enzymes come from? Your DNA, or genes.

We all have the same genes, but we inherit different “versions” of those genes from our biological parents. One gene can have numerous versions, or variants, and each variant will produce a slightly different product… in this case, an enzyme.

Different enzymes perform differently. If the enzyme your body produces functions less efficiently than normal, it can cause problems.

Monoamine Oxidase (MAO)

Of all the genes involved in tyramine metabolism, monoamine oxidase (MAO) plays the largest role, as far as we know. It’s the most discussed enzyme when the topic of tyramine comes up.

MAO is a well-known enzyme in the science world, but not because of its role in tyramine metabolism. MAO also breaks down many “monoamine” neurotransmitters in the body, including serotonin, dopamine, epinephrine, and norepinephrine, which makes it a big player in behavior and especially mental health.

Interestingly, MAO breaks down phenylethylamine (PEA), another amine found in high concentrations in chocolate.

The MAO enzyme actually has two slightly different versions, MAO-A and MAO-B (called isozymes in the science world). Likewise, we have an MAO-A gene and an MAO-B gene. Today, we’ll focus on MAO-A.

The Monoamine Oxidase (MAO-A) Gene

If you have a less efficient variant of the MAO gene, it may put you at higher risk for tyramine intolerance, and other things as well.

There are many ways genes that genes can produce different variants. The best known are SNPs, or single nucleotide polymorphisms. This is a genetic variant that differs by only ONE nucleotide.

If you want to investigate your genes in the context of your health, or understand your 23andMe or similar data, you’ll be investigating SNP data. For a good primer on SNPs, read this.

A given gene can have many different SNPs. If a gene is important in health, science will often investigate many SNPs in one gene to see if they’re associated with disease.

It just so happens that there are several SNPs in the MAO-A gene that scientists have studied at one time or another. Four of them are available in your 23andMe data.

For each SNP, a certain genotype leads to a “low activity” enzyme. And with tyramine intolerance, lower activity may mean slower metabolism of tyramine, which can lead to symptoms.

Let’s look at each of these SNPs, one at a time. I got some of this information from GeneFood, which has an MAO-A page.

rs6323

With this well-studied MAO-A SNP, the G variant results in an enzyme showing typical activity, whereas T results in reduced MAO-A activity. Therefore, since you inherit two copies:

G/G = typical MAO-A activity

G/T = somewhat reduced MAO-A activity

T/T = more reduced MAO-A activity

One study found that the T variant was linked to migraine (PMID 22193458). For more info on this SNP, check out Genetic Lifehacks and SNPedia

rs1137070

For this SNP, the risk allele is T, which codes for a reduced-activity variant. So,

C/C = typical MAO-A activity

C/T = somewhat reduced MAO-A activity

T/T = very reduced MAO-A activity

rs3027399

The risk allele for this SNP is G. So,

C/C = typical MAO-A activity

C/G = somewhat reduced MAO-A activity

G/G = very reduced MAO-A activity

rs909525

The risk allele for this SNP is C. So,

T/T = typical MAO-A activity

C/T = somewhat reduced MAO-A activity

C/C = very reduced MAO-A activity

Other SNPs

There are other MAO-A SNPs of interest as well. One study found that having a C at rs2072743 and a G at rs3027400 was associated with migraine.

My MAO-A Genotypes

SNPGenotypeMAO-A activity
rs6323TTVery reduced
rs1137070CCNormal
rs3027399GGVery reduced
rs909525CTSomewhat reduced

Could my MAO-A SNPs be contributing to my tyramine intolerance? This would suggest yes. However…

Genes are Complicated

Keep in mind that when it comes to tyramine intolerance, monoamine oxidase A (and these SNPS) are only part of the story. Why?

Most people who develop tyramine intolerance don’t do so until they hit middle age. I’m no exception. Our genes don’t change, which means something else has influenced MAO-A activity and the ability to metabolize tyramine.

Also, other genes influence tyramine metabolism as well, which I will cover in other articles. Finally, other factors probably play an important role here, such as gut health. We have enzymes and neurons in the gut too, which could influence tyramine metabolism and the development of symptoms.

Just as importantly, genes are unpredictable creatures. Even if genotype GG in SNP X is associated with syndrome Y, there will always be people with syndrome Y who don’t have GG, and people with GG who don’t have syndrome Y.

But it’s still good to know as much as we can about tyramine intolerance and begin adding more pieces to the tyramine intolerance puzzle.

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The Rogue Scientist

Christie Hartman is a writer and scientist specializing in science-based health. A biology major as an undergrad, she completed her PhD in behavioral genetics at the University of Colorado Boulder. Before starting her writing career, she worked as a scientist and professor at CU’s School of Medicine, where she studied the genetic contributions to substance abuse and antisocial behavior.

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